Pima Indians have a low sympathetic nervous system (SNS) activity and low SNS activity is associated with a greater rate of weight gain. Since glucocorticoids may inhibit SNS activity, we measured SNS and hypothalamic-pituitary-adrenal (HPA) axis activities in non-diabetic Pimas and Caucasians. The activity of the HPA axis was similar in the two groups, indicating that the lower SNS activity in Pima Indians may be the result of a higher sensitivity of the SNS to the inhibitory effect of glucocorticoid i.e. a functional hypercortisolism. Studies to test this hypothesis are just being completed. Finally, using positron emission tomography (PET) we have also studied the neuroanatomical areas of the brain involved in hunger and satiation in humans. Preliminary findings suggest that obese individuals have an attenuated cerebral blood flow increase in the anterior cingulate during hunger and an attenuated blood flood increase in the lateral prefrontal cortex during satiation. This project is terminated.